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1.
Phys Chem Chem Phys ; 18(7): 5192-202, 2016 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-26813691

RESUMO

Femtosecond vibrational spectroscopy was used to probe the rebinding kinetics of NO to microperoxidase-8 (Mp), an ideal model system for the active site of ligand-binding heme proteins, including myoglobin and hemoglobin, after the photodeligation of MpNO in glycerol/water (G/W) solutions at 294 K. The geminate rebinding (GR) of NO to Mp in viscous solutions was highly efficient and ultrafast and negligibly dependent on the solution viscosity, which was adjusted by changing the glycerol content from 65% to 90% by volume in G/W mixtures. The kinetics of the GR of NO to Mp in viscous solutions was well represented by an exponential function with a time constant of ca. 11 ps. Although the kinetic traces of the GR of NO to Mp in solutions with three different viscosities (18, 81, and 252 cP) almost overlap, they show a slight difference early in the decay process. The kinetic traces were also described by the diffusion-controlled reaction theory with a Coulomb potential. Since the ligand is deligated in a neutral form, an ionic pair of NO(-) and Mp(+) may be produced before forming the Mp-NO bond by an electron transfer from Mp to NO as the deligated NO is sufficiently near to the Fe atom of Mp. The strong reactivity between NO and ferrous heme may arise from the Coulomb interaction between the reacting pair, which is consistent with the harpooning mechanism for NO binding to heme.


Assuntos
Óxido Nítrico/química , Peroxidase/química , Análise Espectral/métodos
2.
Bioorg Med Chem Lett ; 25(23): 5625-31, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26508549

RESUMO

Somatic heterozygous mutations of isocitrate dehydrogenase-1 (IDH1) are abundantly found in several types of cancer and strongly implicate altered metabolism in carcinogenesis. In the present study, we have identified α-mangostin as a novel selective inhibitor of mutant IDH1 (IDH1-R132H). We have observed that α-mangostin competitively inhibits the binding of α-ketoglutarate (α-KG) to IDH1-R132H. The structure-relationship study reveals that α-mangostin exhibits the strongest core inhibitor structure. Finally, we have observed that α-mangostin selectively promotes demethylation of 5-methylcytosine (5mC) and histone H3 trimethylated lysine residues in IDH1 (+/R132H) MCF10A cells, presumably via restoring the activity of cellular α-KG-dependent DNA hydroxylases and histone H3 lysine demethylases. Collectively, we provide evidence that α-mangostin selectively inhibits IDH1-R132H.


Assuntos
Descoberta de Drogas , Isocitrato Desidrogenase/antagonistas & inibidores , Xantonas/química , Ligação Competitiva , Humanos , Isocitrato Desidrogenase/genética , Células MCF-7 , Estrutura Molecular , Mutação , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Relação Estrutura-Atividade , Xantonas/farmacologia
3.
J Neuroeng Rehabil ; 11: 139, 2014 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-25240501

RESUMO

BACKGROUND: We examined the effects of the unilateral cortical stimulation on the survival of neurons showing degenerative changes and compared those in delaying the progression of amyotrophic lateral sclerosis (ALS) between the unilateral cortical stimulation and the bilateral one in an animal experimental model using mice. METHODS: We used 19 G93A transgenic mice and randomly divided into three groups: the control group (n=6) (the implantation of electrodes in the bilateral motor cortex without electrical stimulation), the unilateral stimulation group (n=7) (the implantation of electrodes in the unilateral motor cortex with a 24-hour cortical stimulation) and the bilateral stimulation group (n=6) (the implantation of electrodes in the bilateral motor cortex with a 24-hour cortical stimulation). RESULTS: The mean survival period was significantly longer in the bilateral stimulation group as compared with the control group (124.33 ± 11.00 days vs. 109.50 ± 10.41 days) (P<0.05). In addition, on postoperative weeks 11, 12, 13, 14 and 15, the mean Rota-rod score was significantly higher in the unilateral stimulation group as compared with the control group (P<0.05). Furthermore, despite a lack of statistical significance, it was the lowest in the bilateral stimulation group on postoperative weeks 13, 14, 15 and 17. On postoperative weeks 11, 12, 13, 14 and 16, the mean score of paw-grip endurance was significantly higher in the unilateral stimulation group as compared with the control group (P<0.05). Furthermore, despite a lack of statistical significance, it was the lowest in the bilateral stimulation group on postoperative weeks 13, 14, 15 and 17. CONCLUSIONS: In conclusion, our results indicate that the bilateral epidural cortical stimulation might have a treatment effect in a murine model of ALS. But it is the limitation that we examined a small number of experimental animals. Further studies are therefore warranted to establish our results and to identify the optimal parameters of the epidural cortical stimulation in a larger number of experimental animals.


Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Dura-Máter , Terapia por Estimulação Elétrica/métodos , Córtex Motor , Animais , Modelos Animais de Doenças , Progressão da Doença , Masculino , Camundongos , Camundongos Transgênicos
4.
Pain Med ; 14(1): 5-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23241063

RESUMO

BACKGROUND AND OBJECTIVES: Ultrasound-guided cervical periradicular steroid injection (US-CPSI) is an attractive alternate to conventional C-arm guided transforaminal epidural injection for treatment of cervical radicular pain. We compared the technical differences and clinical outcomes between these two techniques. METHODS: Following ultrasound-guided needle placement, the extent of contrast media spread and the degree of tissue penetration were monitored by real-time fluoroscopy at the time of cervical periradicular injection in 59 patients. The spread pattern was judged to be medial foramen (medial bisector of foramen), lateral foramen (lateral bisector of foramen), or extraforaminal. The degree of tissue penetration was classified into periradicular, pararadicular, and intramuscular based on the penetration characteristics. Ultrasonographic images were categorized into crescent, perineuronal protruding, and intramuscular types. These groups were then correlated with clinical outcomes. RESULTS: The actual distance between the ultrasound-guided needle position and fluoroscopic target point was 1.9 and 2.3 cm in the oblique and anteroposterior view, respectively. Despite a difference in ultrasound and fluoroscopic end points, contrast dye spread was found to reach lateral foramen in 53%, medial foramen in 34%, and extraforaminal in 13% of the subjects. Analysis of postprocedural pain reduction (PPPR) showed significantly the better outcomes in periradicular and pararadicular penetration, medial and lateral, and crescent and perineural protruding type without subgroup differences than intramuscular penetration, extraforaminal spread, and ultrasonographic images of intramuscular type (P < 0.001). Analysis of clinical overall outcome showed favorable outcome in the groups with better results of PPPR. CONCLUSION: Our preliminary data suggest that the technique of UP-CPSI can provide an adequate local spread pattern, tissue penetration for treatment of cervical radicular pain.


Assuntos
Meios de Contraste/farmacocinética , Dor/prevenção & controle , Radiculopatia/metabolismo , Radiculopatia/prevenção & controle , Esteroides/administração & dosagem , Esteroides/farmacocinética , Ultrassonografia de Intervenção/métodos , Feminino , Humanos , Injeções Epidurais , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/metabolismo , Medição da Dor/efeitos dos fármacos , Radiculopatia/diagnóstico , Distribuição Tecidual , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
5.
Am J Sports Med ; 51(1): 107-118, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36412925

RESUMO

BACKGROUND: Peripheral tears of the posterior horn of the medial meniscus, known as "ramp lesions," are commonly found in anterior cruciate ligament (ACL)-deficient knees but are frequently missed on routine evaluation. PURPOSE: To predict the presence of ramp lesions in ACL-deficient knees using machine learning methods with associated risk factors. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2. METHODS: This study included 362 patients who underwent ACL reconstruction between June 2010 and March 2019. The exclusion criteria were combined fractures and multiple ligament injuries, except for medial collateral ligament injuries. Patients were grouped according to the presence of ramp lesions on arthroscopic surgery. Binary logistic regression was used to analyze risk factors including age, sex, body mass index, time from injury to surgery (≥3 or <3 months), mechanism of injury (contact or noncontact), side-to-side laxity, pivot-shift grade, medial and lateral tibial/meniscal slope, location of bone contusion, mechanical axis angle, and lateral femoral condyle (LFC) ratio. The receiver operating characteristic curve and area under the curve were also evaluated. RESULTS: Ramp lesions were identified in 112 patients (30.9%). The risk for ramp lesions increased with steeper medial tibial and meniscal slopes, higher knee laxity, and an increased LFC ratio. Comparing the final performance of all models, the random forest model yielded the best performance (area under the curve: 0.944), although there were no significant differences among the models (P > .05). The cut-off values for the presence of ramp lesions on receiver operating characteristic analysis were as follows: medial tibial slope >5.5° (P < .001), medial meniscal slope >5.0° (P < .001), and LFC ratio >71.3% (P = .033). CONCLUSION: Steep medial tibial and meniscal slopes, an increased LFC ratio, and higher knee rotatory laxity were observed risk factors for ramp lesions in patients with an ACL injury. The prediction model of this study could be used as a supplementary diagnostic tool for ramp lesions in ACL-injured knees. In general, care should be taken in patients with ramp lesions and its risk factors during ACL reconstruction.


Assuntos
Lesões do Ligamento Cruzado Anterior , Humanos , Lactente , Lesões do Ligamento Cruzado Anterior/complicações , Estudos de Coortes , Articulação do Joelho/cirurgia , Ligamento Cruzado Anterior/cirurgia , Meniscos Tibiais/cirurgia , Medição de Risco , Estudos Retrospectivos
6.
Korean J Med Educ ; 34(4): 319-325, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36464902

RESUMO

PURPOSE: Using simulation in continuing professional development (CPD) courses for local practitioners is uncommon in Korea. The aim of our study was to evaluate the responses of the local practitioners for a simulation-based short CPD course. METHODS: Following the targeted needs assessment of local practitioners, we developed and implemented a 3-hour simulation-based CPD course for the first 5 minutes of cardiac arrest in the resource-limited local clinics. We evaluated the participant's responses to the course using a questionnaire. RESULTS: During the 3-year implementation period, 115 practitioners participated in 10 courses, and 113 (98%) responded to the questionnaire. The overall course satisfaction (10-point scale) was very positive (10 in 93 [82.3%], 9 in 19 [16.8%], and 8 in 1 [0.8%]). The level (5-point scale) of recommendation to the others was also high (5 in 103 [91.2%] and 4 in 10 [8.8%]). Many participants positively commented on the authentic practical experience of the uncommon crisis in their contexts. CONCLUSION: A simulation-based short CPD course for in-hospital cardiac arrest could provide an authentic practical experience for local practitioners working in resource-limited clinics.


Assuntos
Parada Cardíaca , Humanos , República da Coreia , Avaliação das Necessidades
7.
Pain Med ; 12(1): 36-44, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21087408

RESUMO

OBJECTIVE: Pressure-controlled manometric discography is used by clinicians to evaluate discogenic pain. However, some would improve diagnostic accuracy. The goal of this study was to investigate potential confounding factors that might affect discographic results. Pressure differences depending on different speed of injection, lengths of connecting tubing and locations of sensors were evaluated using an in vitro model system. METHODS: Two sets of automated discography devices were arranged to record post-syringeal pressure pressures (PSPs) and intradiscal pressures (IDPs) in an "air chamber disk model" representing intradiscal pressure. PSPs and IDPs were measured simultaneously while varying injection speeds, and using intrasyringeal and extrasyringeal pressure sensors and contrast medium-filled tubing of different lengths. All pressure/volume curves were collected and viewed dynamically, and stored for further analysis. RESULTS: At injection speed of 0.1 cc/second, the mean pressure difference (mean ΔP) between PSP and IDP was 38.1 psi. As injection speed was reduced, mean ΔP was proportionally decreased. Mean ΔP was 5.3 psi at injection speed of 0.01 cc/second and 0.7 psi at 0.005 cc/second. Mean ΔP values were significantly higher when pressures were recorded using intrasyringeal sensor: at injection speed of 0.1 cc/second, PSP and IDP values were 82.9 and 30.1 psi, respectively, compared with 50.6 and 12.5 psi measured by extrasyringeal sensor. Mean ΔP due to increased length of tubing was not significant. CONCLUSION: Discography can be better performed with low speed injection (≤0.01 cc/second), using an extrasyringeal sensor. Difference of length of connecting tubings did not cause significant pressure differences. These data suggest that automated discography is a helpful adjunct to improve diagnostic accuracy, due to extrasyringeal location of pressure sensor and greater control of injection speed.


Assuntos
Deslocamento do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/patologia , Mielografia/métodos , Dor/diagnóstico , Dor/patologia , Coluna Vertebral/patologia , Algoritmos , Doença Crônica , Meios de Contraste/administração & dosagem , Humanos , Injeções , Manometria , Mielografia/instrumentação , Pressão , Software , Seringas , Resultado do Tratamento
8.
J Chem Phys ; 132(16): 164112, 2010 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-20441263

RESUMO

The excited-state reversible reaction of a neutral particle and a charged particle in an external electric field is studied in three dimensions. This work extends the previous investigation for the ground-state reaction [S. Y. Reigh et al., J. Chem. Phys. 129, 234501 (2008)] to the excited-state reaction with two different lifetimes and quenching. The analytic series solutions for all the fundamental probability density functions are obtained with the help of the diagonal approximation. They are found to be in excellent agreement with the exact numerical solutions of anisotropic diffusion-reaction equations. The analytical solutions for reaction rates and survival probabilities are also obtained. We find that the long-time kinetic transition from a power-law decrease to an exponential increase can be controlled by the external field strength or excited-state decay rates or both.

9.
J Orthop Res ; 38(6): 1279-1288, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31883134

RESUMO

The diagnostic utility of radiographic signs of complete discoid lateral meniscus remains controversial. This study aimed to investigate the diagnostic accuracy and determine which sign is most reliably detects the presence of a complete discoid lateral meniscus in children. A total of 141 knees (age 7-16) with complete discoid lateral meniscus and 141 age- and sex-matched knees with normal meniscus were included. The following radiographic signs were evaluated: lateral joint (LJ) space, fibular head (FH) height, lateral tibial spine (LTS) height, lateral tibial plateau (LTP) obliquity, lateral femoral condyle (LFC) squaring, LTP cupping, LFC notching, and prominence ratio of the femoral condyle. Prediction models were constructed using logistic regressions, decision trees, and random forest analyses. Receiver operating characteristic curves and area under the curve (AUC) were estimated to compare the diagnostic accuracy of the radiographic signs and model fit. The random forest model yielded the best diagnostic accuracy (AUC: 0.909), with 86.5% sensitivity and 82.2% specificity. LJ space height, FH height, and prominence ratio showed statistically large AUC compared with LTS height and LTP obliquity (P < .05 in all). The cut-off values for diagnosing discoid meniscus to be <12.55 mm for FH height, <0.804 for prominence ratio, and >6.6 mm for LJ space height when using the random forest model. On the basis of the results of this study, in clinical practice, LJ space height, FH height and prominence ratio could be easily used as supplementary tools for complete discoid lateral meniscus in children.


Assuntos
Aprendizado de Máquina , Meniscos Tibiais/diagnóstico por imagem , Lesões do Menisco Tibial/diagnóstico por imagem , Adolescente , Criança , Feminino , Humanos , Modelos Logísticos , Masculino , Curva ROC , Estudos Retrospectivos
10.
J Chem Phys ; 131(15): 154105, 2009 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-20568845

RESUMO

Excited-state reversible geminate recombination with two different lifetimes and quenching is investigated in two dimensions. From the exact Green function in the Laplace domain, analytic expressions of two-dimensional survival and binding probabilities are obtained at short and long times. We find that a new pattern of kinetic transition occurs in two dimensions. The long-time effective survival probabilities show a pattern of (ln t)(-1)-->constant-->e(t) depending on the rate constants while the effective binding probabilities show t(-1)(ln t)(-2)-->t(-1)-->e(t).

11.
RSC Adv ; 9(29): 16375-16383, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35516356

RESUMO

Ternary structures consisting of hollow g-C3N4 nanofibers/MoS2/sulfur, nitrogen-doped graphene and bulk g-C3N4 (TCN) were designed as a dual layered film and fabricated using a spin-coating method. The first ternary structures were spin-coated on fluorine-doped tin oxide (FTO) glass, followed by spin-coating of g-C3N4 film to form dual layers. We characterized the microstructural morphologies, chemical composition/bonding and optical properties of the dual layered film and observed significantly reduced recombination rates of photo-induced electron-hole pairs due to effective separation of the charge carriers. We tested methylene blue (MB) photodegradation and observed remarkable MB degradation by the dual layered film over 5 hours, with a kinetic rate constant of 1.24 × 10-3 min-1, which is about four times faster than that of bare TCN film. Furthermore, we estimated the H2 evolution of the dual layered film to be 44.9 µmol over 5 hours, and carried out stable recycling over 45 hours under visible irradiation. Due to the lower electrochemical impedance spectroscopy (EIS) resistance value of the dual layered film (∼50 ohm cm2) compared to the TCN film, the ternary structures and bulk g-C3N4 film were well-connected as a heterojunction, reducing the resistance at the interface between the film and the electrolyte. These results indicate that the effective separation of the photo-induced electron-hole pairs using the dual layered film dramatically improved its photo-response ability under visible light irradiation.

12.
Chemphyschem ; 9(3): 470-4, 2008 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-18232052

RESUMO

Proton and deuteron transfer rates and mechanisms are studied in polar molecular nanoclusters. The cluster environment strongly influences the reaction rate and the nature of these changes is studied as a function of the cluster size. The stabilities of the covalent reactant and polar product states change with cluster size and this effect alters both the equilibrium properties and transfer rate. The proton and deuteron are light quantum particles and the quantum character of the rate process is reflected in the magnitude of the kinetic isotope effect. Our mixed quantum-classical rate simulations indicate that the magnitude of the isotope effect decreases as the cluster size increases. More generally, our study shows how quantum effects combined with structural nanosolvation effects can lead to changes in reaction rates and mechanisms which should be applicable to many quantum charge transfer reactions in molecular nanoclusters.

13.
J Chem Phys ; 129(8): 084102, 2008 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-19044813

RESUMO

The quantum-classical Liouville equation describes the dynamics of a quantum subsystem coupled to a classical environment. It has been simulated using various methods, notably, surface-hopping schemes. A representation of this equation in the mapping Hamiltonian basis for the quantum subsystem is derived. The resulting equation of motion, in conjunction with expressions for quantum expectation values in the mapping basis, provides another route to the computation of the nonadiabatic dynamics of observables that does not involve surface-hopping dynamics. The quantum-classical Liouville equation is exact for the spin-boson system. This well-known model is simulated using an approximation to the evolution equation in the mapping basis, and close agreement with exact quantum results is found.


Assuntos
Teoria Quântica , Algoritmos , Físico-Química/métodos , Simulação por Computador , Elétrons , Modelos Químicos , Modelos Estatísticos , Modelos Teóricos , Oscilometria
14.
J Cerebrovasc Endovasc Neurosurg ; 18(3): 229-233, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27847766

RESUMO

OBJECTIVE: Researchers and clinicians have been unable to fully elucidate the natural course of and proper treatment for unruptured intracranial aneurysms (UIAs) smaller than or equal to 5 mm, particularly with regard to whether close observation or surgery is more appropriate. In this retrospective study, we evaluated the safety and efficacy of endovascular coil embolization of small (≤ 5 mm) asymptomatic UIAs by analyzing outcomes and complications associated with the procedure. MATERIALS AND METHODS: We analyzed data from 150 patients with small asymptomatic UIAs (≤ 5 mm) treated with coil embolization between January 2011 and December 2015. Three-dimensional angiography was used to measure aneurysm size. We evaluated procedure-related morbidity and mortality, immediate post-operative angiographic results, brain computed thomography follow-up results on post-operative day one, and clinical progress. RESULTS: UIAs occurred primarily in the anterior circulation area (142 cases, 94.67%), though eight patients exhibited UIAs of the posterior circulation. Following coil embolization, aneurysms with complete occlusion were observed in 137 cases (91.3%). Partial occlusion occurred in five cases (3.33%), while the procedure had failed in eight cases (5.33%). Procedure-related morbidity and mortality were five cases (3.33%) and zero cases, respectively. CONCLUSION: The endovascular treatment of small asymptomatic UIAs is associated with good short-term outcomes without permanent neurologic complications as well as low overall complication and morbidity rates. Thus, the procedure should be considered for patients with smaller asymptomatic UIAs.

15.
J Cerebrovasc Endovasc Neurosurg ; 18(3): 234-238, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27847767

RESUMO

OBJECTIVE: Endovascular treatment is one of the most important treatments along with open craniotomy for cerebrovascular surgery. The successful treatment of endovascular disease relies on appropriate instruments and the surgeon's skill. Endovascular treatment needs to provide safe and stable access to the catheter cavity. Additionally, it is important to maintain a round shape without changing to an oval shape. The catheter for endovascular treatment has to be flexible and accommodate at least 0.027 inches of inner diameter. The 6-Fr Navien™ Intracranial Support Catheter (formerly the ReFlex Intracranial Catheter; Covidien Vascular Therapies, Mansfield, MA, USA) provides 0.072 inches of inner diameter. MATERIALS AND METHODS: We reviewed 61 cases for 56 cases of endovascular treatment with a Navien catheter. A triaxial system was used for all procedures with femoral arterial access. The Navien catheter was placed in the petrous segment of the internal carotid artery or third segment of the vertebral artery. The patients had various shapes of intracranial arteries, including tortuous vessels. RESULTS: The Navien catheter was used for 61 cases of endovascular treatment. We had 59 cases of coil embolization at unruptured and ruptured aneurysms and two cases of stent insertion into the middle cerebral artery. All the cases were successful without any catheter-related complications. CONCLUSION: The Navien catheter is a recently developed catheter that has several strengths compared with previously developed catheters. It provides a more stable environment for endovascular treatment. It provides a cavity sufficient for endovascular treatment devices. Additionally, it is sufficiently flexible to approach tortuous vessels.

16.
Environ Toxicol Pharmacol ; 20(1): 149-56, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21783582

RESUMO

An organophosphate pesticide terbufos (S-t-butylthiomethyl-O,O-diethyl phosphorodithioate; TBF) has been extensively used as an insecticide. A sexual dimorphism in TBF toxicity was not reported and remains unclear. The objective of the work was to investigate the influence of TBF on sexual dimorphism after oral administration of TBF to rats by using acetylcholinesterase (AChE) and neuropathy target esterase (NTE) as endpoints. TBF was orally administered to Sprague-Dawley rats, where female rats were received 0, 0.1, 0.4 and 0.8mg/kg TBF for 2 days and male rats 0, 0.1, 0.5 and 1.0mg/kg TBF for 3 days for dose-dependent study. Age-matched female and male rats also received equally 0.5mg/kg TBF for 2 days and sacrificed 0, 6, 12, 24 and 72h after the last dose for time-dependent study. In the dose-dependent study, mortality was 25% in 1.0mg/kg TBF group of male and 50% in 0.4 and 0.8mg/kg TBF groups of female rats, resulting in about two-fold higher in female than male. AChE was significantly decreased only in the frontal and entorhinal cortexes of female rats receiving 0.4 or 0.8mg/kg TBF. In the time-dependent study, the maximal inhibition in the brain regions or plasma was two- or three-fold higher in female, which occurred 6 or 12h after the last dose. However, effects of TBF on alteration of NTE activity were minor, compared to AChE, indicating that AChE is more sensitive marker than NTE in TBF toxicity. These results also indicate that female was more vulnerable to AChE inhibition than male rats after exposure to TBF.

17.
J Cancer Prev ; 20(1): 78-83, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25853107

RESUMO

BACKGROUND: Recent genome-wide sequencing studies have identified unexpected genetic alterations in cancer. In particular, missense mutations in isocitrate dehydrogenase-1 (IDH1) at arginine 132, mostly substituted into histidine (IDH1-R132H) were observed to frequently occur in glioma patients. METHODS: We have purified recombinant IDH1 and IDH1-R132H proteins and monitored their catalytic activities. In parallel experiments, we have attempted to find new selective IDH1-R132H chemical inhibitor(s) from a fragment-based chemical library. RESULTS: We have found that IDH1, but not IDH1-R132H, can catalyze the conversion of isocitrate into α-ketoglutarate (α-KG). In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting α-KG into (R)-2-hydroxyglutarate (R-2HG). Moreover, we have identified a new hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one as a new selective IDH1-R132H inhibitor. CONCLUSIONS: We have observed an underlying biochemical mechanism explaining how a heterozygous IDH1 mutation contributes to the generation of R-2HG and increases cellular histone H3 trimethylation levels. We have also identified a novel selective IDH1-R132H chemical hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one, which could be used for a future lead development against IDH1-R132H.

18.
Korean J Neurotrauma ; 10(2): 142-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27169052

RESUMO

Encapsulated acute subdural hematoma (ASDH) has been uncommonly reported. To our knowledge, a few cases of lentiform ASDH have been reported. The mechanism of encapsulated ASDH has been studied but not completely clarified. Encapsulated lentiform ASDH on a computed tomography (CT) scan mimics acute epidural hematoma (AEDH). Misinterpretation of biconvex-shaped ASDH on CT scan as AEDH often occurs and is usually identified by neurosurgical intervention. We report a case of an 85-year-old man presenting with a 2-day history of mental deterioration and right-sided weakness. CT scan revealed a biconvex-shaped hyperdense mass mixed with various densities of blood along the left temporoparietal cerebral convexity, which was misinterpreted as AEDH preoperatively. Emergency craniectomy was performed, but no AEDH was found beneath the skull. In the subdural space, encapsulated ASDH was located. En block resection of encapsulated ASDH was done. Emergency craniectomy confirmed that the preoperatively diagnosed AEDH was an encapsulated ASDH postoperatively. Radiologic studies of AEDH-like SDH allow us to establish an easy differential diagnosis between AEDH and ASDH by distinct features. More histological studies will provide us information on the mechanism underlying encapsulated ASDH.

19.
Nat Commun ; 5: 3351, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24548998

RESUMO

Adenylate kinase 2 (AK2), which balances adenine nucleotide pool, is a multi-functional protein. Here we show that AK2 negatively regulates tumour cell growth. AK2 forms a complex with dual-specificity phosphatase 26 (DUSP26) phosphatase and stimulates DUSP26 activity independently of its AK activity. AK2/DUSP26 phosphatase protein complex dephosphorylates fas-associated protein with death domain (FADD) and regulates cell growth. AK2 deficiency enhances cell proliferation and induces tumour formation in a xenograft assay. This anti-growth function of AK2 is associated with its DUSP26-stimulating activity. Downregulation of AK2 is frequently found in tumour cells and human cancer tissues showing high levels of phospho-FADD(Ser194). Moreover, reconstitution of AK2 in AK2-deficient tumour cells retards both cell proliferation and tumourigenesis. Consistent with this, AK2(+/-) mouse embryo fibroblasts exhibit enhanced cell proliferation with a significant alteration in phospho-FADD(Ser191). These results suggest that AK2 is an associated activator of DUSP26 and suppresses cell proliferation by FADD dephosphorylation, postulating AK2 as a negative regulator of tumour growth.


Assuntos
Adenilato Quinase/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Adenilato Quinase/genética , Animais , Linhagem Celular , Proliferação de Células/genética , Proliferação de Células/fisiologia , Fosfatases de Especificidade Dupla/genética , Eletroforese em Gel Bidimensional , Proteína de Domínio de Morte Associada a Fas/genética , Proteína de Domínio de Morte Associada a Fas/metabolismo , Células HeLa , Humanos , Técnicas In Vitro , Células MCF-7 , Masculino , Camundongos , Camundongos Nus , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Fosforilação , Espectrometria de Massas em Tandem , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Ann Rehabil Med ; 36(5): 596-608, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23185723

RESUMO

OBJECTIVE: To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. METHOD: Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 µs duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. RESULTS: There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. CONCLUSION: Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods.

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